1. Field of the Invention
The present invention relates to a delivery device for delivery of beneficial agents at a controlled rate, and more particularly, the invention relates to osmotic drug delivery systems and methods for enhanced start-up and performance of osmotic drug delivery systems.
2. Description of the Related Art
Controlled delivery of beneficial agents, such as drugs, in the medical and veterinary fields has been accomplished by a variety of methods. One method for controlled and prolonged delivery of beneficial agents involves the use of osmotic delivery systems. These devices can be implanted to release the beneficial agent in a controlled manner over a preselected time or administration period. In general, osmotic delivery systems operate by imbibing fluid from the outside environment and releasing corresponding amounts of the beneficial agent.
Osmotic delivery systems, commonly referred to as "osmotic pumps," generally include some type of a capsule having walls which selectively pass water into an interior of the capsule which contains a water-attracting osmotic agent. The absorption of water by the water-attracting agent within the capsule reservoir creates osmotic pressure within the capsule which causes the beneficial agent to be delivered from the capsule. The water-attracting agent may be the beneficial agent delivered to the patient; however, in most cases, a separate osmotic agent is used specifically for its ability to draw water into the capsule.
When a separate osmotic agent is used, the osmotic agent may be separated from the beneficial agent within the capsule by a movable dividing member or piston. The structure of the capsule is such that the capsule does not expand when the osmotic agent takes in water. As the osmotic agent expands, it causes the beneficial agent to be discharged through an orifice at the same rate as the water enters the osmotic agent by osmosis. Osmotic delivery systems may be designed to deliver a beneficial agent at a controlled constant rate, a varying rate, or in a pulsatile manner.
In known osmotic delivery systems, an osmotic tablet is used as the osmotic agent and is placed inside the capsule. The osmotically active agent and the compartment in which it resides may be referred to as an "osmotic engine." A membrane plug is then placed in an opening in the capsule through which the tablet was inserted. The water enters the capsule through the membrane plug. Alternatively, water may enter directly through the capsule walls if they are permeable to water.
Due to machining and tableting tolerances, the osmotic tablet in the solid initial state is generally sized somewhat smaller than the reservoir in which it is received. Thus, there are air-filled gaps between the osmotic tablet and the surrounding walls of the chamber, between the osmotic tablet and the membrane plug through which water is absorbed, and between the osmotic tablet and the piston. Due to these air-filled gaps, when water begins to be drawn into the osmotic tablet though the membrane plug, the osmotic tablet expands into the surrounding air space and beneficial agent delivery start-up is delayed by a time during which the osmotic tablet expands to fill the air spaces within the chamber. The start-up may be delayed up to several days or weeks depending on the size of the air gaps and the flow rate of the system. Delayed start-up of beneficial agent delivery is a significant problem in osmotic delivery systems.
Another potential problem with known osmotic delivery systems is freezing-up or locking of the osmotic tablet against the sides of the chamber. The osmotic tablet passes through several states from the solid initial state to the hydrated delivery state. As the tablet begins to swell upon wetting it acts more like a solid than a deformable gel. Upon initial wetting, the swelling of the tablet can cause it to lock against the rigid capsule reservoir side walls causing the agent delivery to be delayed until sufficient water has permeated into the osmotic tablet to soften the tablet to the point where it flows. The freeze-up of the osmotic tablet upon initial wetting leads to delayed delivery. In addition, freeze-up can also lead to catastrophic problems such as membrane rupture, expulsion of the membrane plug, or a sudden increase in the delivery rate of the beneficial agent.
Known osmotic delivery systems include those disclosed in U.S. Pat. Nos. 3,797,492, 3,987,790, 4,008,719, 4,865,845, 5,057,318, 5,059,423, 5,112,614, 5,137,727, 5,151,093, 5,234,692, 5,234,693, 5,279,608, and 5,336,057. Pulsatile delivery devices are also known which deliver a beneficial agent in a pulsatile manner as disclosed in U.S. Pat. Nos. 5,209,746, 5,308,348, and 5,456,679. The disclosure of each of the above identified patents is hereby incorporated by reference in its entirety to the same extent as if the language of each patent were specifically and individually incorporated by reference.